Surrogate endpoints facilitate trial efficiency but are variably linked to clinical
outcomes, and limited data are available exploring their utilization in cardiovascular
clinical trials over time. We abstracted data regarding primary clinical, intermediate,
and surrogate endpoints from all phase II to IV cardiovascular clinical trials from
2001 to 2012 published in the 8 highest Web of Science impact factor journals. Two
investigators independently classified the type of primary endpoint. Of the 1,224
trials evaluated, 677 (55.3%) primary endpoints were clinical, 165 (13.5%) intermediate,
and 382 (31.2%) surrogate. The relative proportions of these endpoints remained constant
over time (p = 0.98). Trials using surrogate endpoints were smaller (187 vs 1,028
patients) and enrolled patients more expeditiously (1.4 vs 0.9 patients per site per
month) compared with trials using clinical endpoints (p <0.001 for both comparisons).
Surrogate endpoint trials were independently more likely to meet their primary endpoint
compared to trials with clinical endpoints (adjusted odds ratio 1.56, 95% CI 1.05
to 2.34; p = 0.03). Rates of positive results in clinical endpoint trials have decreased
over time from 66.1% in 2001 to 2003 to 47.2% in 2010 to 2012 (p = 0.001), whereas
these rates have remained stable over the same period for surrogate (72.0% to 69.3%,
p = 0.27) and intermediate endpoints (74.4% to 71.4%, p = 0.98). In conclusion, approximately
a third of contemporary cardiovascular trials use surrogate endpoints. These trials
are completed more expeditiously and are more likely to meet their primary outcomes.
The overall scientific contribution of these surrogate endpoint trials requires further
attention given their variable association with definitive outcomes.
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Article info
Publication history
Published online: March 19, 2016
Accepted:
March 8,
2016
Received in revised form:
March 8,
2016
Received:
January 12,
2016
Footnotes
Drs. Patel and Vaduganathan contributed equally to this manuscript.
The authors had full access to the data, take responsibility for its integrity, and had complete control and authority over manuscript preparation and the decision to publish.
See page 1850 for disclosure information.
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Copyright
© 2016 Elsevier Inc. All rights reserved.
